The present invention relates generally to cytokine receptors and more specifically to granulocyte-colony stimulating factor receptors.
Human Granulocyte-Colony Stimulating Factor (G-CSF) is a lineage-specific hematopoietic protein which stimulates the proliferation and differentiation of granulocyte-committed progenitor cells. Human G-CSF has also been shown to functionally activate mature neutrophils. The cDNAs for human (Nagata et al., Nature 319;415, 1986) and mouse G-CSF (Tsuchiya et al., PNAS 83, 7633, 1986) have been isolated, permitting further structural and biological characterization of G-CSF.
G-CSF initiates its biological effect on cells by binding to specific G-CSF receptor protein expressed on the plasma membrane of a G-CSF responsive cell. Because of the ability of G-CSF to specifically bind G-CSF receptor (G-CSFR), purified G-CSFR compositions will be useful in diagnostic assays for G-CSF, as well as in raising antibodies to G-CSF receptor for use in diagnosis and therapy. In addition, purified G-CSF receptor compositions may be used directly in therapy to bind or scavenge G-CSF, thereby providing a means for regulating the immune activities of this cytokine. In order to study the structural and biological characteristics of G-CSFR and the role played by G-CSFR in the responses of various cell populations to G-CSF or other cytokine stimulation, or to use G-CSFR effectively in therapy, diagnosis, or assay, purified compositions of G-CSFR are needed. Such compositions, however, are obtainable in practical yields only by cloning and expressing genes encoding the receptors using recombinant DNA technology. Efforts to purify the G-CSFR molecule for use in biochemical analysis or to clone and express mammalian genes encoding G-CSFR have been impeded by lack of a suitable source of receptor protein or mRNA. Prior to the present invention, no cell lines were known to express high levels of G-CSFR constitutively and continuously, which precluded purification of receptor for sequencing or construction of genetic libraries for direct expression cloning.